Helicase-Primase Inhibitor Pritelivir for HSV-2 Infection

BackgroundPritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection. MethodsWe randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding. ResultsHSV shedding among placebo recipients was detected on 16.6% of days; shedding among pritelivir recipients was detected on 18.2% of days among those receiving 5 mg daily, 9.3% of days among those receiving 25 mg daily, 2.1% of days among those receiving 75 mg daily, and 5.3% of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95% confidence interval [CI], 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95% CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95% CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95% CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0% in the placebo group to 1.2% in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95% CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95% CI, 0.03 to 0.52). The rate of adverse events was similar in all groups. ConclusionsPritelivir reduced the rates of genital HSV shedding and days with lesions in a dose-dependent manner in otherwise healthy men and women with genital herpes. (Funded by AiCuris; ClinicalTrials.gov number, NCT01047540.) New treatments are needed for herpes simplex virus infection. In this placebo-controlled, randomized, dose-ranging trial, pritelivir, an inhibitor of the viral helicase-primase complex, reduced genital HSV-2 shedding in a dose-dependent fashion. Treatment of genital infections with the herpes simplex virus (HSV) relies on nucleoside analogues that inhibit the HSV DNA polymerase after phosphorylation by the viral thymidine kinase.(1) These compounds, which were developed three decades ago and are in widespread use today, ameliorate clinical disease. However, they do not abrogate viral shedding and only partially reduce the risk of transmission to sexual partners.(2)-(4) In immunocompromised persons, resistance to nucleoside analogues develops occasionally, and treatment options for acyclovir-resistant HSV are limited.(5),(6) The thiazolylamide pritelivir (BAY 57-1293; AIC316) is the first in a new class of antiviral agents that inhibit HSV ...